In the United States in 1997, it has been estimated that there were more than 26,000 new cases of cancer of the ovary, and that approximately 14,000 women died from it, making it the most lethal of the gynecological malignancies. Close to 2 percent of women are affected during their lifetimes. Ovarian cancer is difficult to treat because patients frequently present late in the disease course, which may be asymptomatic until advanced stages. The few established risk factors do not appear to account for a large fraction of disease incidence, and the possible mechanisms by which these factors affect risk of developing ovarian cancer are still not well understood. Based upon a substantial body of pathologic, endocrinology and epidemiologic evidence, we have recently suggested a new hormonal hypothesis regarding the etiology of ovarian cancer. To examine this hypothesis, we are conducting, in the state of Connecticut, a population-based case-control interview study which will examine a collection of factors related to hormonal expression during and after the reproductive years. In total, about 580 ovarian-cancer cases aged 35-79 years are being identified prospectively in the state through our Rapid Case Ascertainment system, and 1,000 randomly selected population controls are being frequency matched to the cases in three age groups. We now propose to analyze buccal-smear cell samples collected from all of the study subjects, in order to examine whether certain known, common, germline genetic polymorphism variants in the hormones and hormonal mechanisms under study are associated with altered risk of ovarian cancer. PCR methods will be used for the genetic analyses. In general, the hormonal factors being examined have received only a little attention with respect to ovarian cancer, and our ongoing project is the first to evaluate them systematically in a rigorous, large-scale study which will integrate all of the factors within a coherent etiologic framework. The new study proposed here will substantiate, through genetic considerations, the risk associations seen for the hormonal climate manifestations considered in our existing study, and may provide further insight into possible etiologic mechanisms of ovarian cancer.